What are the functional consequences of CDKL5 dysregulation in patient derived neuronal cells?

Research Opportunity
Honours, Master of Biomedical Science
Number of Honour Places Available
1
Number of Master Places Available
1
Department
Paediatrics
Location
Royal Children’s Hospital/Murdoch Childrens Research Institute
Primary Supervisor Email Number Webpage
Doctor Nicole Van Bergen nicole.vanbergen@mcri.edu.au Personal web page
Co-supervisor Email Number Webpage
Professor John Christodoulou john.christodoulou@mcri.edu.au Personal web page

Summary This project will contribute to our investigations on the critical role of the mammalian CDKL5 protein in neurons. CDKL5 is a kinase that regulates key phosphorylation events on many proteins.

Project Details

The Cyclin-Dependent Kinase-like 5 (CDKL5) protein is critical for neuronal function and differentiation. CDKL5 Deficiency Disorder (CDD) is an X-linked developmental encephalopathy that results in early onset and difficult to control seizures and severe neurodevelopmental impairment, leading to lifelong disability. The CDKL5 protein is expressed in the brain, predominantly in neurons and regulates key phosphorylation events that in turn regulate cell proliferation, neuronal maturation, synaptic activity, neuronal network function and the movement of subcellular cargo in neurons.  This project will contribute to our investigations on the critical role of the mammalian CDKL5 protein in neurons. CDKL5 is a kinase that regulates key phosphorylation events on many proteins. Some recently identified targets of CDKL5 in neuronal cells include microtubule proteins, however only a few targets have been discovered, leaving many potential targets yet to be identified. The phosphorylational regulation of microtubules is very important as it will affect neuronal maturation, synaptic activity, and neuronal network function and the movement of subcellular cargo in neurons. This project will validate potential new targets regulated by CDKL5. These targets will be validated using complementary in vitro techniques.   We will validate potential CDKL5 targets using a combination of standard biochemical and molecular biology techniques including, but not limited to cell culture, qPCR, SDS-PAGE immunoblotting, phospho-specific western blotting, cloning, co-immunoprecipitation, immunofluorescence and enzyme assays.   We will identify key pathways regulated by CDKL5 and which will improve our understanding of how this kinase regulates synaptic activity in brain-like neural networks. This project will for the first time provide a comprehensive and detailed understanding of the CDKL5 kinase in neuronal cell biology. Our project will provide future opportunities for drug design and therapeutics targeting kinase activity.



Faculty Research Themes

Child Health

School Research Themes

Child Health in Medicine



Research Opportunities

Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Paediatrics

Research Node

Royal Children’s Hospital/Murdoch Childrens Research Institute

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